Molecular and Cellular Neuroscience Commons^™

Assessing The Role Of Drosophila Melanogaster Neuroligin 3 On Social Spacing And Climbing Behaviour, J. Wesley Robinson

Electronic Thesis and Dissertation Repository

Autism spectrum disorders can be clinically defined in part by impairments of social interactions. Social interactions can be modeled in Drosophila melanogaster with behaviours such as social spacing. Here, I examined the effects of autism-related gene neuroligin 3 on fly social spacing. I hypothesized if neuroligin 3 is mutated or gene expression is targeted for knockdown, then flies will have altered social space in males and females at different ages. Using the social space assay, I found that different mutations to neuroligin 3 change the fly’s behavior, in a mutation and sex-specific manner. Using an antibody against Nlg3, I localized …

The Functional And Structural Analysis Of Drosophila Robo2 In Axon Guidance, Lafreda Janae Howard

Graduate Theses and Dissertations

In animals with complex nervous systems such as mammals and insects, signaling pathways are responsible for guiding axons to their appropriate synaptic targets. Importantly, when this process is not successful during the development of an organism, outcomes include catastrophes such as human neurological diseases and disorders. It is vital to determine the underlying causes of such diseases by understanding the development of the nervous system. There are many pathways that have been identified to play a role in this, however, we lack an understanding of how these pathways can promote such diverse outcomes in different populations of neurons. These pathways …

Novel Characterization Of The Role Of Orthologous Xap5 In Caenorhabditis Elegans, Nabor Vazquez

Lawrence University Honors Projects

Cilia are one of the oldest and most well conserved cellular organelles. Cilia provide an essential role in cellular locomotion, fluid regulation, and are a site for signal transduction pathways involved in sensation. A new study suggests that XAP5 is a transcription factor in a unicellular organism, Chlamydomonas reinhardtii, which regulates gene expression needed for proper cilium assembly. Our study investigates the conservation of the role of XAP5 in a multicellular system, Caenorhabditis elegans. Alignments between protein, coding region, and promoter sequences for XAP5 orthologs from related species show a good conservation in DNA and protein sequences. As part of …

Detecting The Cold: Do Innexins Function In Cold Nociception?, Rachel Barborek

Senior Honors Projects, 2010-2019

Nociception is the perception of and response to harmful stimuli. Nociception is essential for minimizing tissue damage, but aberrant nociceptive pathways can result in chronic pain. Chronic pain in the U.S. is commonly managed with wide-acting opioids, and precisely defining the components of nociceptive pathways could uncover novel targets for pain therapies. I hypothesize that the vitally quick process of nociception would utilize electrical synapses because they transmit signals between neurons more quickly than chemical synapses do. This study, therefore, aims to uncover the potential role of the eight Drosophila melanogaster gap junction proteins, the Innexins, in cold nociception. Wild …

Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph Loturco Phd

University Scholar Projects

Brain tumors are the most common childhood solid malignancy, and because of remarkable advances in treating many cancers outside of the brain, they have become the leading cause of cancer mortality in children. Ependymomas are a class of brain tumors which can be further subdivided into three groups based upon their location and genetic features. Of the three classes, supratentorial ependymomas are the only subgroup known to be marked by an oncogenic driver gene, which consists of a fusion mutation between the C11orf95 and RELA genes. C11orf95-RELA positive tumors are the most aggressive and lethal of …

Quantifying Expression Of Interneuron Subtype Markers For Dlx-2 Transfected Ng2 Cells, Timothy Nolan

Honors Scholar Theses

Neurons are a post-mitotic cell population, and therefore, they are not able to regenerate in vivo after a traumatic injury. Because inhibitory GABAergic interneurons and oligodendrocyte precursor cells (OPCs) are derived from the same precursor, recent studies have focused on transforming these OPCs into GABAergic neurons. However, there are different types of GABAergic interneurons that have different electrophysiological responses, which can lead to functional differences. The Nishiyama laboratory had already used a key gene in GABAergic interneuron and OPC differentiation, Distal-less homeobox 2 (Dlx-2), to transfect OPCs; early electrophysiology tests showed most of these transfected cells behaved like immature neurons, …

A Novel Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Synapse Development, Hao Wu

Dissertations, Theses, and Capstone Projects

Cytoskeleton based active transport with motor proteins is essential for mRNA localization and local protein translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased screen for interaction between mRNA binding proteins (RBP) and motor proteins, we identified protein interacting with APP tail 1 (PAT1) as a potential direct adapter between the β-actin mRNA Zipcode-binding protein 1 (ZBP1) and Kinesin-1 motor complex.

Mouse PAT1 is similar to the Kinesin Light Chain (KLC) in amino acid sequence and binds directly to KLC. High-resolution images from structured illumination microscopy (SIM) indicates that synaptic stimulation …

Circadian Rhythmicity And Neurodevelopment Of Disco And Grim Mutations In Drosophila Melanogaster, John Patrick Story

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

The death gene grim and its pathway for apoptosis has been studied extensively in Drosophila Melanogaster. The effects of grim mutations on circadian neurodevelopment and locomotor assays have yet to be investigated. Mutations in the gene disconnected (disco) has been shown to disrupt the normal development of the circadian circuitry, specifically the small ventro-lateral neurons (s-LNv’s). Which has shown to severely decrease rhythmicity during free-running periods. Alternatively, we have observed an increase in rhythmicity during free-running periods in grim mutations. Our goal is to investigate the neurodevelopment of the circadian circuitry and their associated locomotor activities in these Drosophila mutations.

Investigating Comt Influence On The Proactive-Reactive Stress Coping Axis In Zebrafish, Sean T. Bresnahan, Ryan Y. Wong

UNO Student Research and Creative Activity Fair

Individuals of the same species often display differences in correlated suites of behaviors which are made conspicuous when challenges – stressful, fear-inducing, etc. – are presented. In many species, a specific suite of behaviors (risk-aversion, aggression, exploration, learning, and memory) characterize an alternative set of stress coping styles (proactive and reactive). Such behaviors are regulated in the brain by specific neurotransmitters along with proteins that regulate them. One neurotransmitter regulator protein, catechol-O-methyltransferase (COMT) shows higher baseline whole-brain expression in proactive relative to reactive animals. However, it is not known whether its expression is a cause or a consequence of the …

The Role Of H3k4 Methyltransferases In Drosophila Memory, Nicholas Raun

Electronic Thesis and Dissertation Repository

Gene transcription required for long-term memory requires the modification of histones. However, there are still many uncertainties about the identity and spatial expression of genes regulated by histone modifications during memory related processes. In this project I examined the role of Drosophila melanogaster methyltransferases Set1 and trx in courtship memory. Genetic knockdown of Set1 and trx in the mushroom body (MB) revealed that Set1 was necessary for short- and long-term memory, while trx was only required for long-term memory. Transcriptional profiling of MBs following trx-knockdown revealed expression changes in MB-enriched genes and genes involved in RNA processing. Among the …

Mutations Of Fus Cause Aggregation Of Rna Binding Proteins, Disruptions In Protein Synthesis, And Dysregulation Of Nonsense Mediated Decay, Marisa Elizabeth Kamelgarn

Theses and Dissertations--Toxicology and Cancer Biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron death and subsequent muscle atrophy. Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma (FUS) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. FUS undergoes liquid- liquid phase transition in vitro, allowing for its participation in stress granules and RNA transport granules. Phase transition also contributes to the formation of cytoplasmic inclusions found in the …

Glial Cell Mechanisms Regulate Alcohol Sedation In Drosophila Melanogaster, Kristen M. Lee

Theses and Dissertations

Approximately 16 million people in America are diagnosed with Alcohol Use Disorder (AUD) but no efficacious medical treatments exist. Alcohol-related behaviors can be studied in model organisms, and changes in these behaviors can be correlated with either (i) a risk for alcohol dependence or (ii) a symptom/feature of AUD itself. Although AUD is a disease of the central nervous system, a majority of research has focused on the neuronal underpinnings, leaving glial contributions largely undescribed. We used Drosophila melanogaster (fruit fly) to identify genes whose expression in glia regulates alcohol sedation. Mammals and Drosophila have conserved behavioral responses to alcohol …

Investigating Neurogenesis As A Veritable Epigenetic Endophenotype For Alzheimer's Disease, Layne Wells

Scripps Senior Theses

Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by progressive amyloid plaque aggregation, neurofibrillary tangles, and cortical tissue death. As the prevalence of AD is projected to climb in coming years, there is a vested interest in identifying endophenotypes by which to improve diagnostics and direct clinical interventions. The risk for complex disorders, such as AD, is influenced by multiple genetic, environmental, and lifestyle factors. Significant strides have been made in identifying genetic variants linked to AD through the genome-wide association study (GWAS). It has been estimated in more recent years, however, that GWAS-identified variants account for limited …